MAKCIN 100MG

Indications

• Serious Gram-negative infections resistant to gentamicin
• Neonatal sepsis
• Pseudomonal lung infection in cystic fibrosis

Dosage

Children: Child 1 month–11 years: 7.5 mg/kg every 12 hours; Child 12–17 years: 7.5 mg/kg every 12 hours, increased to every 8 hours if necessary. Neonate: 15 mg/kg every 24 hours.

Adults: Refer to BNF for specific adult dosing guidelines.

Mechanism of action

Amikacin works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit, causing misreading of mRNA and disrupting the production of essential proteins, leading to bacterial cell death.

Pharmacodynamics

Amikacin exhibits concentration-dependent bactericidal activity against a broad spectrum of Gram-negative bacteria, including Pseudomonas aeruginosa. The efficacy of amikacin is influenced by the peak concentration and the time above the minimum inhibitory concentration (MIC).

Pharmacokinetics

Amikacin is primarily eliminated by renal excretion. It has a volume of distribution of approximately 0.25 to 0.4 L/kg and a half-life of about 2 to 3 hours in patients with normal renal function. Dosage adjustments are necessary in renal impairment to prevent accumulation and toxicity.

Contra-indications

• Myasthenia gravis

Adverse effects

• Ototoxicity
• Nephrotoxicity
• Hearing loss
• Tinnitus
• Renal impairment
• Confusion
• Lethargy
• Anaemia
• Bronchospasm
• Eosinophilia
• Fever
• Headache
• Hypomagnesaemia
• Paraesthesia

Interactions

• Other nephrotoxic drugs
• Neuromuscular-blocking agents

Precautions

• Care must be taken with dosage (dose-related effects)
• Correct dehydration if possible
• Monitor serum-amikacin concentrations, especially in renal impairment
• Avoid use in patients with renal impairment unless necessary

Pregnancy

There is a risk of auditory or vestibular nerve damage in the infant when aminoglycosides are used during the second and third trimesters of pregnancy.

Breast-feeding

Aminoglycosides are excreted in breast milk; caution is advised.

Storage

Store in a cool, dry place away from direct light.

Formulations

• Intravenous injection
• Intravenous infusion
• Intramuscular injection

Mechanism of action

The primary mechanism of action of amikacin is the same as that for all aminoglycosides. It binds to bacterial 30S ribosomal subunits and interferes with mRNA binding and tRNA acceptor sites, interfering with bacterial growth. This leads to disruption of normal protein synthesis and production of non-functional or toxic peptides. Other actions have been postulated for drugs of this class. Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal against gram-positive and gram-negative bacteria. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Pharmacodynamics

Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, however, other antibiotics may be more potent and less toxic to humans.